Enveloped viruses deliver their genomes to cells by fusing with cellular membranes. This fusion process is mediated by viral envelope glycoproteins when they undergo conformational changes while binding target cells. Our research goals are to understand structure-function relationships in the envelope glycoprotein in order to provide information for the rational design of novel HIV inhibitors and vaccines. We have undertaken mutagenesis studies (in press, Journal of Virology) of a highly conserved coiled domain in the transmembrance protein which our previous studies indicate could be a broadly neutralizing epitope. We found that this region is intolerant to most mutations suggesting that antibodies that bind this region are unlikely to generate escape mutants. We are making novel gp41 immunogens to test whether focusing the immune response on structures containing the coiled region will generate broadly neutralizing antibodies. To date we have found that antibodies raised against an isolated helical domain recognize intact envelope glycoprotein. High quality, efficient and credible review of vaccines requires scientific expertise in many areas. This research provides highly specialized knowledge about HIV envelope glycoprotein structure-function relationships and humoral responses to the envelope glycoprotein. In addition, this work provides more general expertise relating to vaccine development including antibody generation and characterization, virus isolation and propagation, infectivity studies and virus neutralizations.